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EDITORIAL
Year : 2019  |  Volume : 37  |  Issue : 1  |  Page : 1-4
 

Vaccines as a tool to contain antimicrobial resistance


WHO Regional Office for South-East Asia Region, New Delhi - 110 002, India

Date of Web Publication16-Aug-2019

Correspondence Address:
Rajesh Bhatia
WHO Regional Office for South-East Asia Region, New Delhi - 110 002
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmm.IJMM_19_223

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How to cite this article:
Bhatia R. Vaccines as a tool to contain antimicrobial resistance. Indian J Med Microbiol 2019;37:1-4

How to cite this URL:
Bhatia R. Vaccines as a tool to contain antimicrobial resistance. Indian J Med Microbiol [serial online] 2019 [cited 2019 Sep 23];37:1-4. Available from: http://www.ijmm.org/text.asp?2019/37/1/1/264493




Antimicrobial agents, commonly called as antibiotics, and vaccines have been two cost-effective and proven technological tools that revolutionised humanity's battle with infectious diseases. The impact of these interventions has been phenomenal in reducing mortality and morbidity across the world. These are widely hailed as the two greatest accomplishments of modern medicine which have saved the most lives globally.[1]

Both the vaccines and the antibiotics act against causative agents of infectious diseases. However, their mechanisms of action and some other characteristics differ. Antibiotics are therapeutic tools, and vaccines are preventive that have been responsible for elimination/eradication. Antibiotics are short-acting tools and vaccines accord long-duration memory. The combination of these tools has been phenomenally successful in containing infectious diseases.

These two tools, along with sanitation and safe water, brought down significantly the incidence of infectious diseases during the last century in many developed countries. The success was mainly due to the continuous development of newer and efficacious antibiotics during the 1960s. Impressed with the impact of antibiotics, the then Surgeon General of the USA made a famous statement[2] that the 'time has come to close the book on infectious diseases.' However, as we know, it was not to be. Infectious diseases continue to be major individual and public health challenges in most countries of the world. Two reasons for this are survival instinct of bacteria and indiscriminate the use of antibiotics, which is the greatest driver of making bacteria resistant.

The survival instinct in bacteria generated several mechanisms in bacteria that conferred resistance to antibiotics.[3] The resistance also started appearing rapidly and cumulatively giving rise to multi-antibiotic-resistant variants. Although a large number of antibiotics were discovered during the past eight decades, resistant has emerged to almost all of these.[4]


 ~ Antimicrobial Resistance and Its Implications for Human Health and Development Top


This antimicrobial resistance (AMR) has been defined as unresponsiveness to antibiotics when administered in standard doses. It has serious implications for a patient,[5] treating physician and health system as management of diseases due to resistant pathogens is difficult, expensive, prolonged and negates the impact of modern complex surgeries [Table 1].
Table 1: Impact of antibiotics-resistant pathogens on human health

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The implications of AMR are huge at global level, adversely impacting the human development. The cost of inaction to contain AMR has been quantified. As compared to current estimated 700,000 annual deaths due to resistant pathogens,[6] around 10 million people will succumb annually to diseases due to resistant pathogen by 2050[7] if no concerted actions are initiated now. This number shall be greater than those who will die due to road accidents and cancers put together. Within the same time frame, global gross domestic product will decrease by 3.5% and a cumulative financial loss of USD 100 trillion is anticipated.[7] The World Bank[8] has warned that AMR has the potential to reduce livestock production by 7.5%, thus impacting global food security. An additional 28 million people will be pushed below the poverty line, and global exports will also suffer a serious setback of reduction of 3.8% by 2050.[8]

The global action plan on AMR,[9] developed by the World Health Organisation (WHO) and endorsed by the Food and Agriculture Organization of the United Nations,[10] World Organization for Animal Health[11] and the United Nations General Assembly,[12] proposes a strategic road map to combat AMR. It includes surveillance, awareness, rational use of antibiotics, infection prevention and control and research. It also emphasises on implementing all those measures that reduce the burden of infectious diseases. Vaccines can play a critical role in reducing the burden of diseases as well as that of resistant pathogens.


 ~ Potential Role of Vaccines in Reducing Antimicrobial Resistance Top


Vaccines have huge potential in reducing AMR [Figure 1] directly and indirectly by reducing the burden of pathogens including the resistant subpopulations, the transfer of genetic material encoding resistance between different organisms, diminishing the virulence of few pathogens (e.g., Bordetella pertussis) and at times conferring herd protection even in the unvaccinated population. Thus, the spread of antimicrobial-resistant infections is also restricted.[13]
Figure 1: Mechanism of reduction in antimicrobial resistance due to vaccines

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Through these actions, vaccines significantly reduce the use of antibiotics by preventing bacterial infections and viral infections (such as measles, influenza and varicella), for which bacterial secondary infections are common. Vaccines also reduce the misuse of antibiotics by preventing viral diseases, for which antibiotics are inappropriately prescribed, including influenza and rotavirus diarrhoea.

Extensive use of several of these vaccines has successfully demonstrated above-mentioned benefits of vaccination against bacterial and viral diseases.


 ~ Impact of Bacterial Vaccines on Disease Epidemiology and Antimicrobial Resistance Top


Bacterial meningitis and related diseases due to  Neisseria More Details meningitidis, Haemophilus influenzae and Streptococcus pneumoniae have been dramatically reduced in several countries with significant coverage with respective polysaccharide vaccines that have been conjugated with products of diphtheria or tetanus bacteria to induce longer and stronger immunity.

A meta-analysis of AMR in meningococci in Africa had shown the prevalence of resistance to penicillin (17.9%), chloramphenicol (4.6%) and co-trimoxazole (50.1%).[14] A vaccine was created using the diseases causing strain of meningococcus serogroup A and used extensively in several African countries. It reduced meningitis due to the serogroup A N. meningitidis by 99% in the countries that opted to use it to immunise younger children.[15] The number of meningitis epidemics at district level reduced by 60% following vaccination.[16] This vaccine also decreased bacterial carriage and induced herd immunity.[15] Before 1990, H. influenza e Type b had started exhibiting resistance to commonly used antibiotics, especially ampicillin, forcing the use of chloramphenicol and cephalosporins for empirical treatment of meningitis. The vaccination not only reduced disease burden but also pre-empted the continuing evolution of AMR, including a major impact on unvaccinated persons through herd immunity.[17]

Meningitis and related bacterial infections due to H. influenzae Type b were also substantially reduced in several countries with the introduction and extensive coverage of its vaccine.[18] In Italy, H. influenzae Type b conjugate vaccine with an uptake of >95% by 2011 could reduce the rate of hospitalisation due to invasive disease from 2.3 in 2001 to 0.9 × 100,000 among children 1–4 years and from 5.4 in 2001 to 2.4 × 100,000 among infants.[18] In Gambia, invasive disease due to H. influenzae Type b was almost eliminated following the introduction of the H. influenzae Type b conjugate vaccine.[19]

Extensive work has been documented to demonstrate the impact of pneumococcal conjugate vaccines (PCVs) in reducing the prevalence of diseases due to this organism, reduction in the use of antibiotics and drug-resistant pathogens. With a vaccine coverage of 94%, Iceland showed a high efficacy of the vaccination on vaccine serotypes. It also demonstrated a milder effect on vaccine-associated-serotype 6A. Importantly, there was a significant herd effect on vaccine types in older non-vaccine-eligible children. Overall, antimicrobial non-susceptibility was also reduced.[20]

In Northern California, introduction of a PCV prevented 35 antibiotic prescriptions per 100 vaccinated children, suggesting that 1.4 million antibiotic prescriptions per year are preventable with PCV in the USA.[21] Similarly, in the USA, after the introduction of PCV into the routine childhood immunisation programme, the incidence of penicillin non-susceptible invasive pneumococcal disease decreased by 81% in children younger than 2 years.[22]

Using PCV9, invasive pneumococcal disease due to penicillin-resistant pneumococci and co-trimoxazole-resistant pneumococci was reduced in South Africa by 67% and 56% as compared to unvaccinated control population.[23] With PCV7, Japan could reduce the proportion of penicillin-resistant isolates of pneumococci by 54.7%.[24]

Typhoid fever continues to be a major global public health problem, especially in developing countries. Appearance and accumulation of resistance to commonly used and affordable antibiotics are making its management challenging. It is estimated that around 15 million cases of typhoid fever occur every year.[25]

Multidrug resistance has been rampant in typhoid bacilli[26] and is likely to accentuate in days to come. The WHO opines that the multidrug-resistant typhoid bacilli cause more severe illness, greater mortality and prolonged asymptomatic carrier status.[27]

Three vaccines are currently available against typhoid fever. These include an oral Ty21a vaccine and an injectable which comprises Vi polysaccharide. A tetanus toxoid conjugated Vi vaccine that has recently been produced in India and prequalified by the WHO in 2017 can be administered even to children in 6 months–2 years age group.[28] The reason ascribed for their limited use in the developing countries is their not-so-optimal efficacy which ranges between 50% and 60%. However, recent mathematical models have shown that a vaccine coverage of around >80% with vaccination of populations such as 9 months, 6 years and 12 years old should lead to a >85% reduction in typhoid incidence.[28] In another study, it has been postulated that with 80% vaccination coverage, 44% of the total cases were averted over 10 years. Vaccination also decreased both the total number and proportion of chronic carriers of antimicrobial-resistant infections.[29]

There is obviously a great need to rethink and deploy these vaccines in the national immunisation programmes in enteric fever endemic countries to reduce the burden of typhoid fever as well as drug resistance associated with it.


 ~ Impact of Viral Vaccines on Disease Epidemiology and Antimicrobial Resistance Top


Measles has been responsible for significant morbidity and mortality, mainly because of secondary bacterial infections of the gastrointestinal and respiratory tract, many of which may be due to antibiotic-resistant pathogens. Measles vaccination is one of the most cost-effective health interventions ever developed. Without the vaccine, five million children would die each year from measles, assuming an estimated case, fatality rate of 2%–3%.[30]

Measles vaccine has averted ≥21 million deaths of children between 2000 and 2017.[31] In a multicountry study, measles vaccination was associated with reduction in acute respiratory infection (ARI) cases by 15%–30% in India and Pakistan, and diarrhoea cases by 12%–22% in the Democratic Republic of Congo, India, Nigeria and Pakistan.[32] Prevention of superinfections has reduced burden of bacterial infections and associated AMR.

Viral ARIs influenza vaccines not only prevent viral pathogenesis but also prevent secondary bacterial infections as well as the administration of antibiotics. A study conducted in Canada demonstrated that influenza-associated antibiotic prescriptions declined by >64% after the introduction of influenza vaccination in Ontario.[33] Similarly, in a multicentric trial in Europe, 50% reduction in antibiotic use was observed in children receiving influenza vaccine vis-a-vis unvaccinated controls.[13] The Centers for Disease Control (CDC) estimates that for the 2016–2017 flu season, influenza vaccination of 47% population prevented an estimated 5.3 million illnesses in the USA. An addition of 5% coverage in vaccination rate could have prevented another 483,000 influenza illnesses in the USA.[34]

Rotavirus vaccines are now available across the world. Their efficacy has been estimated to be 70%.[35] India has also launched the vaccination of children in selected areas. It is hoped that it will reduce not only hospitalisation, morbidity and mortality due to rotavirus infections, but also have an impact on reduction in the use of antibiotics for acute diarrhoea in children.


 ~ Challenges and Way Forward Top


Role of vaccines in reducing the burden of infectious diseases and antibiotic-resistant pathogens has been well established. However, vaccines are not available for several important pathogens. The WHO and CDC have identified several pathogens which are important causes of community-acquired or healthcare-associated infections including methicillin-resistant Staphylococcus aureus, Acinetobacter, Klebsiella,  Escherichia More Details coli, Pseudomonas aeruginosa, Clostridium difficile,  Neisseria gonorrhoeae More Details and Mycobacterium tuberculosis and requires research, discovery and development of new tools on priority.[36],[37] Unfortunately, no vaccine is available against any of these pathogens, while few are in varying stages of development and clinical trials.[7]

Better use of available vaccines is also a challenge. Community awareness is not optimal because of lack of awareness, social resistance and unfounded apprehensions of adverse reactions.[38] The improvement in coverage, expansion of spectrum of vaccines package and active engagement with communities is key to success in reducing disease burden and AMR. This needs a multipronged action by policy makers, professionals, researchers and communities and will go a long way in the global fight against AMR.[39]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 ~ References Top

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